Magnesium and trace element oxide premix for animal nutritional supplementation, and manufacturing method

Abstract

The invention relates to a synergistic premix for animal nutrition in the form of a ternary solid of magnesium and a trace element. The premix may consist essentially of a solid solution of a magnesium oxide and a trace element oxide, the trace element being chosen from among iron, copper, zinc and manganese. This premix can be obtained by a method comprising a step of preparing a dry mixture of a raw material of trace element oxide and a raw material of magnesium oxide, then a step of heating the mixture of raw materials to a temperature of 700°C to 1500°C.

Description

Description Title of the invention: Premix of trace element oxide and magnesium for animal nutritional supplementation, and manufacturing method Technical Field

[0001] The invention relates to a nutritional supplement for animals, intended to provide trace elements as a supplement to the diet. It also relates to a method for its manufacture. Prior art

[0002] To address diseases and high mortality rates caused by deficiencies and / or toxicities, the food industry offers mineral supplements that are essential for livestock and profitable for the sector.

[0003] All living beings have a digestive tract beginning at pH = 6-8 controlled mainly by saliva. Food then passes into the stomach at pH = 2-3 except for ruminants, for which the food first undergoes bacterial fermentation in the rumen. After leaving the stomach, food arrives in the intestine at pH 6-7 where it is bio-assimilated.

[0004] The absorption or bio-assimilation of minerals, defined as the fraction of the chemical element passing from food to the portal blood circulation, takes place mainly through the intestinal mucosa, with the exception of magnesium, which is absorbed almost entirely at the level of the reticulo-rumen in ruminants.

[0005] A trace element deficiency in the body causes a chronic or episodic deficiency leading to more or less severe symptoms. This deficiency is frequently observed in animals, because trace elements are generally poorly absorbed by the body at the duodenum level, due to several factors. Indeed, the proteins and fibers in the ration, precipitating agents and mineral competition limit bioassimilation by the body by complexing the trace elements in ionized form.

[0006] Zinc, as well as other trace elements, is poorly assimilated, mainly due to molecular complexations occurring in the stomach of animals. Indeed, trace element salts administered as a supplement to the ration have high dissolution kinetics in an acidic environment, so that the trace element solubilized in cationic form complexes with the organic matter present in the stomach and can no longer reach the bioassimilation zone. The ionized trace element binds in the stomach to chelating agents present in the ration such as phosphates, oxalates, fats and high molecular weight peptides before reaching the duodenum, which leads to a significant decrease in the bioassimilated quantities.Among the chelating agents, phytic acids and their basic forms (phytates) are phosphorus compounds naturally present in cereals and legumes in the food ration, which engage in bonds with minerals such as iron, zinc, copper, cobalt or even manganese, for. create insoluble complexes upon leaving the stomach, so that the trapped minerals are no longer bio-assimilable in the duodenum. Indeed, the pH influences the solubility of the mineral-phytate complexes formed: in the case of zinc, for example, zinc-phytate complexes are insoluble at pH values ​​above 4.3.

[0007] An objective of the present invention is to provide a supplementation tool which improves the bio-assimilation of trace elements, and which makes it possible to reduce the quantity of trace element added to the ration without affecting the functional performance of the animal.

[0008] Prior art supplements are subject to improvement given the limited bio-assimilation of certain trace elements, even in the case of excessive intakes. A large part of these intakes are not utilized by animals and are released into the environment, thus leading to negative ecological consequences. For example, soil contamination by minerals such as zinc in large poultry, pig and cattle farms has been documented. To reduce environmental pollution linked to the intake of zinc in the food industry, it would therefore be desirable to improve the bioavailability of zinc.

[0009] There is therefore a need to use more environmentally friendly trace element food supplements, the use of which involves limited soil contamination.

[0010] Still from an ecological perspective, it would be beneficial if the trace element supplement could be manufactured using a preparation process with limited impact on the environment.

[0011] The strategy of providing excess trace elements in the ration to compensate for their low bioavailability has been adopted by the majority of food industry players. However, the risks of overdosing are not without danger for the animal's health.

[0012] The diversity of zinc sources used in animal nutrition is significant. The raw materials used as a source of zinc in animal nutrition are mainly zinc sulfate and zinc oxide. For example, zinc oxide is estimated to account for 80% of the zinc source in poultry farming.

[0013] Many means have been proposed in the prior art to improve the bioavailability of inorganic zinc sources.

[0014] A first approach consisted of modifying the raw material by proposing nano-Zinc, zinc oxide with a high specific surface area or microencapsulated zinc salts.

[0015] Another strategy proposed in the prior art has been to add bioavailability enhancers to the inorganic zinc source, such as sugars, animal proteins, and polysaccharides, which can improve the bioavailability of the mineral. Organic zinc sources used in supplementation in the form of complexes, chelates, proteinates, or polysaccharides generally lead to better bioavailability than inorganic sources, but their manufacturing cost remains high.

[0016] The use of organic zinc sources, such as zinc glycinate, has also been proposed. However, since the zinc content of organic solutions cannot exceed 25% by mass due to the number of atoms present in the organic molecule, premix formulators favor inorganic zinc sources to retain the possibility of adding supplements and thus being able to offer multi-functional supplements. In addition, these products are relatively expensive.

[0017] It would therefore be desirable to offer a trace element supplement that is more economically profitable for breeders, and which makes it possible to limit the quantity of trace element administered to the animal with equal zootechnical performance. Statement of the invention

[0018] The invention meets these needs and relates to a synergistic premix for animal nutrition comprising a ternary solid of magnesium, trace element and oxygen, which may be in the form of a solid solution of a magnesium oxide and a trace element oxide, said trace element being chosen from iron, copper, zinc and manganese.

[0019] The inventors surprisingly discovered that the synergistic premix comprising a ternary solid of magnesium, trace element and oxygen, which may be in the form of a solid solution of a trace element oxide and a magnesium oxide, improves the penetration of the trace element through intestinal cells in vitro, and demonstrates better availability compared to the trace element oxide alone, at an equivalent dose.

[0020] The synergy of action between the two oxides makes it possible to delay the solubilization kinetics of the trace element, and to limit the complexation of the latter by the organic matter of the ration at the stage of digestion in the stomach, for example its complexation with phytates. The premix of the invention therefore makes it possible to maximize the probability of absorption of the trace element at the level of the duodenum by synergy with magnesium, which acts as a support and a means of physical protection of the trace element in the digestive tract.

[0021] The premix of the invention comprising a trace element has the advantage of being manufactured by a process carried out using the dry route, the environmental impact of which is reduced compared to solvent-phase processes.

[0022] In a particular embodiment, the invention provides a food supplementation tool which improves the bio-assimilation of trace elements such as zinc in animals, in particular livestock such as ruminants, poultry and pigs.

[0023] The premix of the invention can be very advantageously administered in an amount such that the daily intake of trace element in the ration is lower than the doses of trace element oxide practiced in the prior art, without affecting the performances functional characteristics of the animal, in particular growth performance, weight gain, feed efficiency, feed conversion index and nutrient assimilation.

[0024] The premix of the invention has the further advantage of reducing the quantity of zinc released into the environment, and of helping to limit pollution of soil, water and the food chain by heavy metals.

[0025] The inventors have surprisingly discovered that the synergistic premix of the invention delays the solubilization of trace element salts, and can consequently remedy the unfavorable complexations which occur at acid pH between the solubilized trace elements and certain molecules of the food ration. The premix of the invention, with adequate solubilization kinetics, makes it possible to increase the proportion of trace elements in ionic form at the end of the passage through the stomach, just before arrival in the intestine, and thus makes it possible to increase the bioavailability of the trace elements.

[0026] In the premix of the invention, the trace element oxide has suitable solubility kinetics, solubilization being delayed in the stomach but sufficiently rapid to make the trace element available in ionic form at the exit of the stomach, before entering the place of absorption, the intestine.

[0027] The inventors surprisingly discovered that using a magnesium-based compound can increase the absorption of zinc. Brief description of the drawings Figure 1 represents the quantities of zinc measured in the feces of piglets supplemented either with a ZnO-MgO mixture according to the invention, or with a ZnO of the prior art. Figure 2 represents the curve of the evolution of the pH value of a hydrochloric acid solution comprising a ZnO-MgO mixture according to the invention or a comparative mixture. Description of the embodiments

[0028] The invention relates to a synergistic premix for animal nutrition, said premix comprising magnesium oxide and a trace element. The premix may be a ternary solid comprising magnesium atoms and trace element atoms.

[0029] For the purposes of the invention, a trace element is understood to mean a chemical element in ionic or atomic form chosen from zinc, copper, cobalt, manganese, iron, iodine and selenium. Magnesium is a macroelement, not a trace element.

[0030] The term "ternary solid" means a crystalline mineral solid comprising at least one crystalline phase in which magnesium atoms, trace element atoms and atoms of a third element are distributed. In a particular embodiment, the ternary solid is a ternary oxide of magnesium and at least one trace element chosen from iron, copper, zinc and manganese. By "at least one" is meant one or more.

[0031] The molar ratio between magnesium and trace element in the ternary solid is preferably greater than 1 and greater than 0.1.

[0032] The ternary solid preferably consists essentially of atoms of magnesium, oxygen, a trace element and possibly phosphorus, hydrogen, carbon and sulfur. The ternary solid may have the chemical formula (Mg x X y Y z ), Y representing O, CO3, OH, SO4H2PO4, or PO4, X representing a trace element atom chosen from iron, copper, zinc and manganese, and x, y and z being decimal numbers. The ternary solid can thus be a ternary oxide when Y represents O, or a ternary phosphate when Y represents P3O4.

[0033] The word "essentially", in particular the word "essentially consisting" in this description, whatever the characteristic to which it refers, a quantity greater than a value chosen from 90%, 95%, 98% or 99%, the percentage being able to be expressed in mass, in moles or in volume.

[0034] The crystalline form of the ternary oxide may be the same as or different from the crystalline form of a chemical compound of magnesium comprising oxygen atoms, such a compound being referred to as "a magnesium oxide" in the remainder of this description, magnesium oxide (MgO) being a particular magnesium oxide.

[0035] In the present description, the term "magnesium oxide" means a material comprising magnesium and oxygen atoms. A magnesium oxide may comprise magnesium hydroxide, magnesium carbonate, magnesium oxide, magnesium carbonate, or a mixture thereof. For example, a magnesium oxide within the meaning of the invention comprises magnesium oxide (MgO), magnesium carbonate (MgCO3), magnesium phosphate (comprising Mg, P, O and optionally H), magnesium hydroxide (Mg(OH)2), and their hydrates.

[0036] In a particular embodiment, the crystalline form of the ternary oxide may be different from the crystalline form of magnesium oxide (MgO), such as the crystalline form of periclase. The crystalline form of the ternary oxide may be different from the crystalline form of an oxide of the trace element. Finally, the ternary oxide preferably consists essentially of magnesium, oxygen and said trace element.

[0037] When the trace element is zinc for example, the ternary oxide may have a crystalline form different from that of a magnesium oxide, and different from that of a zinc oxide (i.e. a compound comprising zinc atoms and oxygen atoms), the zinc oxide being for example chosen from ZnO (zinc oxide), ZnCO3 (zinc carbonate), zinc hydroxycarbonate, and ZnSO4 (zinc sulfate).

[0038] According to a particular embodiment of the invention, the ternary solid is a solid solution, more particularly a substitution solid solution.

[0039] "Solid solution" means a homogeneous solid in which a magnesium oxide, such as magnesium oxide, and a trace element oxide, such as oxide of trace element, form a single crystalline phase. The observation of the crystalline structure and the homogeneity of the solid solution and / or those of the premixture can be carried out under a microscope using a method known to those skilled in the art.

[0040] The solid solution may be a substitution solid solution of the trace element in a magnesium oxide, such as magnesium oxide. A "substitution solid solution" means a solid solution in which atoms of the trace element take the place of magnesium atoms in the crystal lattice of the solid solution.

[0041] Thus, the synergistic premix for animal nutrition of the invention comprises a solid solution essentially consisting of a magnesium oxide and a trace element oxide, said trace element being chosen from iron, copper, zinc and manganese. The solid solution may be a solid solution of substitution of the trace element in a crystalline magnesium oxide, a magnesium oxide being chosen from magnesium oxide (MgO), magnesium carbonate (MgCO3), a magnesium phosphate (comprising Mg, P, O and optionally H), or magnesium hydroxide (Mg(OH)2). In the premix of the invention, the magnesium may advantageously provide physical protection of the trace element, such as zinc for example. Magnesium advantageously serves as a support, a biological vector or a dissolution retardant of the trace element in the digestive tract of an animal.

[0042] The molar amount of the trace element in the premix can vary.

[0043] For example, when the trace element is zinc, zinc can represent from 1% to 45% by mole of the premix. When the trace element is copper, copper can represent from 1% to 25% by mole of the premix.

[0044] The quantity of the trace element in the ternary solid, expressed in moles or in mass, is advantageously greater than a limit value chosen from the group consisting of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%.

[0045] When the trace element is zinc, zinc may represent from 1% to 45% by mole, preferably from 3% to 45% by mole, or even from 10% to 45% by mole of the ternary solid. Zinc may represent from 10% to 45% by mole of a solid solution consisting of magnesium, oxygen and zinc.

[0046] When the trace element is copper, the copper may represent from 1% to 40% by mole, preferably from 3% to 25% by mole, or even from 10% to 25% by mole of the ternary solid of the ternary solid. In a particular case, the copper may represent from 10% to 25% by mole of a solid solution consisting of magnesium, oxygen and copper.

[0047] When the trace element is iron, the iron may represent from 1% to 45% by mole, preferably from 3% to 40% by mole, or even from 10% to 30% by mole of the ternary solid. Iron may represent from 10% to 30% by mole of a solid solution consisting of magnesium, oxygen and iron.

[0048] When the trace element is manganese, the manganese may represent from 1% to 45% by mole, preferably from 3% to 40% by mole, or even from 10% to 30% by mole of the solid ternary. Manganese can represent from 10% to 30% by mole of a solid solution consisting of magnesium, oxygen and manganese.

[0049] The invention also relates to a method for manufacturing a synergistic premix for animal nutrition, said method comprising a step of heating a mixture comprising a powdery raw material of a magnesium oxide, and a powdery raw material of a trace element, in particular a powdery raw material of a trace element oxide. The heating step may also be referred to as sintering or heat treatment in the present description.

[0050] The magnesium oxide raw material is of food grade. The magnesium oxide raw material is of food grade in that it meets the requirements of European Regulation 767 / 2009 concerning the placing on the market and use of animal feed, European Directive 2002 / 32 / EC and Regulations (EU) No 574 / 2011 and (EU) No 277 / 2012 concerning the levels of substances undesirable for animal nutrition. In particular, the amount of magnesium oxide in the raw material is greater than or equal to 70%, for example between 70% and 99%, and the content of heavy metals is less than 500 ppm, more preferably less than 350 ppm.

[0051] In a particular embodiment, the magnesium oxide raw material comprises a content, expressed by mass or by mole, of less than 10%, preferably less than 5%, more preferably less than 1%, of a trace element chosen from iron, copper, zinc and manganese.

[0052] As raw material, magnesium oxide, magnesia MgO, magnesium carbonate, magnesium hydroxycarbonate such as hydromagnesite (Mg5(CO3)4(OH)2,4 H2O), magnesium sulfate, magnesium phosphate, magnesium chloride, magnesium hydroxide or one of their hydrates can be used.

[0053] In one embodiment of the invention, the particle size value of the magnesium oxide raw material and the particle size value of the trace element oxide raw material are preferably less than 200 microns.

[0054] “Particle size value” means a value chosen from the maximum value of the particle size distribution, the D50 value of the particle size distribution (50% of the particles of the raw material having a diameter less than the D50 value), the D90 value of the particle size distribution (90% of the particles of the raw material having a diameter less than the D90 value), the D99 value of the particle size distribution (99% of the particles of the raw material having a diameter less than the D99 value), and the value of the mesh size of the raw material. The particle size value can be measured by any method known to those skilled in the art.

[0055] The value of the particle size of the magnesium oxide raw material is preferably less than 200 microns, for example less than 100 microns, or even less than 50 microns or 25 microns.

[0056] In a particular embodiment, the D50 of the magnesium oxide raw material is less than 100 microns.

[0057] The D90 and / or D99 of the magnesium oxide raw material can be less than 200 microns.

[0058] Examples of magnesium oxide raw material are the MgO product marketed by Sigma-Aldrich (Code: 342793 and CAS: 1309-48-4) with a purity greater than 99% and a mesh size of approximately 44 micrometers (equivalent to 235 mesh), and magnesium hydroxycarbonate (Honeywell reference 63062, CAS 39409-82-0) with an equivalent purity in MgO > 70%, containing less than 50 ppm of zinc and a density of 2.16 g / cm3 (20 °C).

[0059] The magnesium oxide raw material can also be chosen from the Timag Reactive® FT2013 product, the Timag MAG® PEV product, the Brazamag® HR FT 2421 product and the Brazamag® FT 2402 product, all marketed by the Timab Magnesium company.

[0060] In one embodiment, the magnesium oxide raw material is magnesia.

[0061] The value of the particle size of the magnesia is for example such that the D50 is less than a value chosen from 100 microns, 50 microns and 25 microns. In this embodiment, the D90 or the D99 of the magnesia may also be less than 200 microns.

[0062] The magnesia is preferably a caustic magnesia obtained by calcining magnesium carbonate at a temperature between 900°C and 1300°C. The caustic magnesia may comprise, in addition to MgO, impurities such as CaO, SiO2, Fe2O3 and AI2O3.

[0063] The raw material for a trace element oxide is preferably food grade, the definition of the term "food grade" being in accordance with the definition given above.

[0064] The raw material of a trace element oxide is preferably characterized by a minimum value of the mass percentage of trace element chosen from 60%, 70%, 80% or even 90%, the mass percentage being expressed relative to the mass of the raw material.

[0065] In one embodiment of the invention, the particle size value of the trace element oxide raw material is less than 200 microns, for example less than 100 microns, or even less than 50 microns or 25 microns. The definition of the term "particle size value" in the context of describing the trace element oxide raw material is consistent with the definition of the term given above in the context of describing the magnesium oxide raw material.

[0066] The raw material of a trace element oxide preferably has an impurity content, expressed by mass or mole, of less than 10%, preferably less than 5%, relative to the quantity of trace element raw material.

[0067] The raw material of a trace element oxide has, for example, at least one of the following physicochemical characteristics: a particle size value of less than 200 microns, a trace element content of more than 60% by mass, or an impurity content of less than 10% by mass.

[0068] The raw material of a trace element oxide may predominantly comprise a trace element oxide. The term "trace element oxide" means a material comprising atoms of the trace element, oxygen, and optionally sulfur, carbon and hydrogen. The raw material of a trace element oxide may be a raw material comprising a trace element hydroxide, a trace element carbonate, a trace element oxide, a trace element carbonate, or a mixture thereof.

[0069] In the case of zinc for example, the trace element oxide can thus be chosen from ZnO (zinc oxide), ZnCO3 (zinc carbonate), zinc hydroxycarbonate such as for example hydrozincite Zn5(CO3)2(OH)6, and ZnSO4. In a particular embodiment, the trace element oxide is ZnO.

[0070] Examples of zinc oxide raw material are the ZnO product supplied by the company Acros Organics under the reference Zinc oxide, ACS Reagent® (CAS: 1314-13-2), zinc hydroxycarbonate sold by Sigma Aldrich under the reference Zinc Carbonate Basic® with the formula [ZnCO3]2-[Zn(OH)2]3 (CAS: 5263-02-5) or granulated zinc oxide brand ZnO-KB® sold by the supplier Silar.

[0071] The amount of zinc oxide raw material is preferably chosen so that the zinc element represents, for example, from 1% to 40% by mole of the sum of the number of moles of the zinc element of the zinc oxide raw material, and the number of moles of the magnesium element of the magnesium oxide raw material.

[0072] In the case of iron, the trace element oxide can be chosen from FeCO3, FeO, Fe2O3, Fe3O4, FeHO2, Fe4H6O9. Iron carbonate can be anhydrous or hydrated. An iron oxide raw material can be Fe2O3 with a purity greater than 95% and a particle size value less than 5 microns.

[0073] When the trace element is manganese, the trace element oxide may be chosen from MnCO3, MnO, Mn2O3, MnO2, Mn3O4, Mn(OH)2. Manganese carbonate may be anhydrous or hydrated.

[0074] Finally, a copper oxide can be chosen from CuCO3, CuO, Cu2O and Cu(OH)2, the copper carbonate being able to be anhydrous or hydrated.

[0075] The trace element raw material, used in particular as a source of trace element oxide, may be any natural mineral raw material known to those skilled in the art comprising the trace element or a trace element oxide. The raw material will have undergone, after extraction, physical treatments such as grinding, screening, granulation, leaching, purification, chemical treatment, drying, calcination and sieving.

[0076] In one embodiment of the invention, the particle size of the trace element oxide raw material, and the particle size of the magnesium oxide raw material, both defined as D90, are less than 200 microns.

[0077] The heating step of the method of the invention may comprise a temperature increase from room temperature to a plateau temperature ranging from 700°C to 1500°C, maintaining the plateau temperature for a period ranging from 1 hour to 600 hours, and a temperature decrease from the plateau temperature to room temperature. The maximum temperature reached during sintering is preferably between 1100°C and 1500°C, in particular in the case of a zinc oxide raw material.

[0078] The rate of temperature rise and / or fall is in particular between 5°C / min and 30°C / min, for example between 10°C / min and 20°C / min. The total duration of the heat treatment is advantageously between 1 h and 600 h, preferably between 3 h and 48 h.

[0079] In addition to the sintering step, the method of the invention may comprise a subsequent step consisting of an annealing step. This annealing step may be followed by an overprotection step with magnesium hydroxycarbonate (hydromagnesite).

[0080] The present application also relates to a premix capable of being obtained by the manufacturing process described above.

[0081] A synergistic premix for animal nutrition may be obtainable by a process comprising a step of preparing a mixture consisting of dry mixing, preferably at room temperature, a raw material of trace element oxide and a raw material of magnesium oxide, then calcining the mixture.

[0082] The premix of the invention may be obtainable by a method comprising a step of preparing a mixture consisting of dry mixing a raw material of powdered food-grade trace element oxide and a raw material of powdered food-grade magnesium oxide, then a step of heating said mixture to a temperature ranging from 700°C to 1500°C in a closed container, in the absence of water, for a period ranging from 1 to 600 hours, for example for a period ranging from 3 to 48 hours.

[0083] The premix of the invention can take various forms including a lick bucket, a lick block, a powder, a suspension or a solution. It can be introduced directly into the animal's ration or drink.

[0084] Alternatively, it may be formulated into a food or dietary supplement that includes other ingredients.

[0085] The invention thus relates to a nutritional supplement for non-human animals comprising the premix described above, and a compound chosen from vitamins, probiotics, macro-element salts, trace element salts, enzymes and amino acids.

[0086] The invention will also have as its subject a method for preparing a food ration for a non-human animal, comprising a step of dry incorporation of the premix according to claim 1 with fodder and / or cereals.

[0087] The premix of the invention is intended for feeding livestock or breeding animals, in particular ruminants, poultry, pigs, and any other animal species for which zinc supplementation is desirable.

[0088] The premix doses of the invention may vary depending on the species, and depending on the type of production in the case of livestock farming, for example milk and / or meat. The doses may also vary depending on the stage of production at which the livestock farm is located. Those skilled in the art will be able to adapt the necessary doses depending on the intended use.

[0089] For example, ruminants are fed mainly on fodder and a little cereals, but since the magnesium intake from fodder often remains too low, systematic mineral supplementation is recommended for these animals, the recommended daily intake being in the order of 100 mg / kg to 10 g / kg of dry matter (or mg / kg DM) of the ration, for example 300 mg / kg DM to 500 mg / kg DM (or ppm DM).

[0090] In species that consume more cereals, such as pigs and poultry, magnesium can be used occasionally, as needed, with a recommended daily intake of 600 ppm and 1000 ppm DM respectively.

[0091] Zinc supplementation may be recommended for female ruminants to ensure reproductive performance, but also for poultry and pigs. The recommended zinc intake is similar for these three species and ranges from 30 ppm to 150 ppm.

[0092] In accordance with Regulation EC 1095 / 2016, the intake of zinc in feed may be limited to 150 mg Zn / kg of complete feed for piglets, sows, rabbits and fish, to 200 mg Zn / kg of complete feed for cats and dogs, and to 120 mg Zn / kg for other species.

[0093] The premix of the invention makes it possible to obtain at least one biological effect in a non-human animal, this effect being able to be a beneficial effect on the animal's breeding performance. Indeed, a synergy of action between magnesium oxide and trace element oxide is observed.

[0094] The biological, non-therapeutic effect may be selected from increasing the animal's weight gain, supporting the animal's growth, improving feed efficiency, improving the feed conversion ratio, and supporting nutrient assimilation. The invention relates, for example, to the use of the premix described above for increasing the weight gain of an animal, preferably at the beginning of weaning.

[0095] The non-human animal is chosen in particular from livestock, racing animals, and domestic animals, such as for example poultry, crustaceans, fish, dogs, cats, horses, rabbits, sheep, goats, ruminants and pigs.

[0096] One embodiment of the invention relates generally to the use of an amount of premix to achieve a significant increase of at least 5%, or even at least 10%, in a biological performance effect in an animal, compared to the biological effect achieved with an equal amount of trace element oxide raw material.

[0097] The "quantities" within the meaning of the invention which relate to the uses of the premix are molar quantities expressed in moles of trace element or mass quantities, the mass quantities being able to be those of the premix or those of a trace element oxide.

[0098] Another embodiment of the invention relates to the use of an amount of premix of the invention for obtaining a biological performance effect in an animal and / or a value of this effect, which is identical to that obtained with an equal amount of trace element oxide raw material.

[0099] The present description also proposes the use of the premix described above to reduce the quantities of trace elements which are released by animals into the environment via feces, and / or to limit the pollution of livestock soils by trace elements, which may be heavy metals.

[0100] The premix of the invention can be used to obtain at least one biological effect which is significantly improved in comparison with the same biological effect of a trace element source of the prior art, at identical doses of trace element in the premix of the invention and dose of trace element in the trace element source, in the sense that the molar number of trace element in the dose of premix of the invention and the molar number of trace element in the dose of trace element source are identical. The trace element source of the prior art is for example chosen from inorganic salts of trace elements and organic salts of trace elements.

[0101] The biological effect can be chosen from the penetration of the trace element through the intestinal cells; the limitation of complexation of the trace element with the organic matter contained in the digestive tract, in particular, the limitation of complexation of the trace element with phytates; the increase of the bioavailability of the trace element; the delayed release of the trace element in the body; the delay of the solubilization kinetics of the trace element oxide in the stomach; and the increase of the absorption of the trace element at the level of the duodenum.

[0102] The ternary solid allows in particular a delayed release of the trace element. In comparison, a trace element which is not in the form of a ternary solid does not cause a delay in dissolution and undergoes very rapid, almost instantaneous solubilization in an acidic medium.

[0103] For example, a ternary solid which is capable of being obtained by heating at a temperature ranging from 700°C to 1500°C a powdery mixture of a magnesium oxide raw material and a trace element oxide raw material advantageously exhibits kinetics of release of the trace element in bioassimilable form which is delayed in comparison with a reference product, which corresponds to the powder mixture used to prepare the ternary solid. According to a particular embodiment, the ternary solid makes it possible to delay the release of the trace element in an acidic medium, typically in an acidic solution whose initial pH is between 1.0 and 2.0.

[0104] For the purposes of the invention, the term "delayed release" means a start of release of the trace element in bioassimilable form contained in the ternary solid which is later than that of the trace element which is contained in the reference product. The term "delayed release" may also correspond to a duration at the end of which at least 90% by mole of the trace element contained in the ternary solid are released, said duration being greater than the duration at the end of which at least 90% by mole of the trace element contained in the reference product are released.

[0105] According to a particular embodiment, the delayed release kinetics are evaluated in vitro by dissolving the ternary solid in an acid solution whose initial pH is between 1.0 and 2.0. The dissolution of the trace element in the acid solution can occur in a window ranging from 30 s to 300 s, for example from 50 s to 250 s, from the introduction of the ternary solid into the acid solution, while the reference product mentioned above begins to dissolve as soon as the ternary solid is introduced into the acid solution. The time after which the value of the quantity of trace element dissolved from the solid solution reaches the value of the quantity of trace element dissolved from the product can be advantageously increased by at least 50 s, preferably by at least 100 s, and more preferably by at least 150 s.

[0106] In particular, the premix of the invention containing a ternary oxide of zinc and magnesium makes it possible to obtain an effect superior to that of zinc oxide alone, with equal quantities of zinc in the premix and in the zinc oxide, administered to an animal.

[0107] The premix of the invention containing zinc as a trace element can have particularly advantageous solubilization kinetics, defined according to the following conditions, T0 being the moment of introduction of the premix of the invention into a hydrochloric acid solution at pH=2.5: - total insolubilization of Zn 2+ (molar concentration of Zn 2+ zero) between T0 and T100 minutes, and total solubilization of Zn 2+ at T 120 minutes, - solubilization of Zn 2+ less than 50 mol%, preferably less than 40 mol%, at T 30 minutes and total solubilization at T120 minutes.

[0108] The present application describes a synergistic premix for animal nutrition, said premix comprising a solid solution essentially consisting of a magnesium oxide and a trace element oxide, said trace element being chosen from iron, copper, zinc and manganese, the premix being capable of being obtained by the method comprising a step of preparing a mixture consisting of dry mixing a raw material of powdered food grade trace element oxide, and a raw material of powdered food grade magnesium oxide, then a step heating said mixture to a temperature ranging from 700°C to 1500°C in a closed container, in the absence of water, for a period of 3 to 48 hours. The particle size of the trace element oxide raw material, and the particle size of the magnesium oxide raw material, both defined as D90, are advantageously less than 200 microns. The solid solution may be a solid solution of substitution of the trace element in magnesium oxide. When the trace element is zinc, and the zinc may represent from 1% to 45% by mole of the premix. When the trace element is copper, and the copper may represent from 1% to 25% by mole of the premix.

[0109] The invention will be described in more detail in the following examples. Unless otherwise stated, the temperature is between 20°C and 25°C, and the pressure is equal to 1 bar.

[0110] Example 1: Preparation of a premix according to the invention comprising zinc: ZnO-MaO 47.6% by mass of [ZnCO3]2.[Zn(OH)2]3 (CAS: 5263-02-5) supplied by Sigma-Aldrich and 52.4% by mass of MgO (CAS: 1309-48-4) of 99% purity also supplied by Sigma-Aldrich were dry mixed. The mixture was heated from room temperature to 1000°C in a container at a rate of 20°C / min and then kept at this temperature for 16 hours. The amount of Zn in the resulting premix was 25 mol%.

[0111] Example 2: Preparation of a pre-melanae according to the invention comprising iron: Fe2O3-MaO We dry mixed 45.8% by mass Fe2O3 (CAS: 1345-25-1) with a purity > 96% and a particle size <5 pm supplied by Sigma-Aldrich, and 54.2% by mass MgO (CAS: 1309-48-4) with a purity of 99% also supplied by Sigma-Aldrich. The mixture was brought from room temperature to a temperature equal to 950°C in a closed container at a rate of 12°C / min, then maintained at this temperature for 4 hours. The amount of Fe in the obtained premix was 30 mol%.

[0112] Example 3: Preparation of a premix according to the invention comprising copper: CuO-MoO 25.8% by mass Cu(II)O (CAS: 1317-38-0) from batch 329902 / 1 supplied by Fluka Chemika (purity greater than 98%) and 74.2% by mass of MgO (CAS: 1309-48-4) of 99% purity also supplied by Sigma-Aldrich were dry mixed. The mixture was brought from room temperature to a temperature equal to 870°C in a closed container at a rate of 7°C / min, then maintained at this temperature for 4 hours. The amount of Cu in the obtained premix was 15 mol%.

[0113] Example 4: Preparation of a premix according to the invention comprising manganese: MnO-MgO Dry blended 43% by mass Mn(II)O (CAS: 1344-43-0) with a purity greater than 99% supplied by Sigma-Aldrich and 57% by mass MgO (CAS: 1309-48-4) with a purity of 99% also supplied by Sigma-Aldrich. The mixture was brought from room temperature to a temperature equal to 950°C in a closed container at a rate of 20°C / min, then maintained at this temperature for 6 hours. The amount of Mn in the obtained premix was 30 mol%.

[0114] Example 5: In vitro digestion test of the premixture according to the invention ZnO-MgO, and comparison with the prior art The objective of this test was to determine the solubility of zinc in feed supplemented with different zinc salts, including the ZnO-MgO premix of the invention. Specifically, zinc solubilization was compared in an in vitro digestion model, using the premix of Example 1, commercial reference standard zinc oxide ZnO 72% from Arkop, commercial reference zinc oxide HiZox® from Animine, zinc sulfate with a purity greater than 99%, or ECO Trace® brand zinc glycinate manufactured by Biochem. Dissolution protocol: This in vitro model makes it possible to reproduce the chemical conditions that apply to a food passing through the digestive tract of an animal. Indeed, the pH, the retention time, the nature and intensity of the constraints are important parameters to take into account when evaluating the bioavailability of zinc. The parameters chosen for the Mg solubilization protocol 2+ and Zn 2+ were established by comparison with the data collected in the literature relating to the stomach of ruminants. Thus, the volume of the abomasum is approximately ten liters and our considered volume in the reactor is 200 milliliters. The introduced mass of product makes it possible to lead to the equivalent concentration of 5000 ppm of the element in the reaction medium. The pH of the abomasum being generally between 2 and 3, the pH of the reaction medium in the laboratory is fixed at 2.5 by adding hydrochloric acid at a flow rate of up to 10 mL / min to simulate the supply of gastric juice into the stomach. The reaction medium is maintained at 39-40°C corresponding to the internal temperature of the species considered. More precisely, a 200 mL solution of hydrochloric acid at pH=2.5 is prepared in a 1 liter beaker. This beaker is placed in a water bath heated to 40°C, itself positioned on a stirring plate. An automatic titrator is programmed to bring the pH back to 2.5 with a maximum flow rate of 10 mL / min with a pH control range equal to 0.5. The titrator is filled with a 0.1 mol / L hydrochloric acid solution. The 20 mL dosing pump is rinsed 3 times with the 0.1 mol / L hydrochloric acid solution. The pH-metric probe of the titrator is then calibrated with a pH=7 buffer and a pH=4 buffer. The electrode and the injector are then positioned in the solution to be analyzed, taking care to put the injector in contact with the solution to reduce response times. 1 gram of the solid sample is then introduced into the 200 mL HCl solution at pH=2.5. Stirring is started at the same time as a stopwatch and the titrator. Stirring is carried out using a four-centimeter magnetic bar in order to stir as much of the beaker surface as possible. The experiment is carried out over two hours by taking 2 mL of solution at different kinetic times. The volumes taken with the syringe are then filtered through 0.45 pm filters, then 125 pL of the filtered solution is introduced into a 200 mL flask. Finally, 10% of the flask volume is completed with the strontium solution, then the flask is topped up to the mark with distilled water. Sample preparation: The feed consisted of a typical pig mix: 33% wheat, 32% corn, and 35% soybean meal. The feed was first ground and then mixed with each zinc oxide source in a Lodige® mixer for 60 seconds. Each zinc salt was supplemented at a level of 1640 ppm in the feed. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to determine the homogeneity of the mixture. - In vitro digestion protocol The supplemented food was subjected to in-vitro digestion comprising two stages: in a pre-stomach solution at pH=7.0, then in a gastric solution at pH=2, and finally in an intestinal solution at pH=7.0. Thus, the initial volume of solution considered was 200 mL and 10 grams of the supplemented food were introduced for each test at T0. After 30 min, a 5 mL sample was taken and centrifuged at 4000 rpm for 40 min at T=4°C. The zinc content in the supernatant (zinc ions and chelated zinc ions in solution) was determined by ICP-MS. The zinc content in the remainder was also determined to verify general preservation. Two zinc oxides and one zinc sulfate were compared to the ZnO-MgO premix in in vitro digestion. The percentage of solubilized zinc was measured after 30 minutes in order to compare the different zinc salts. Indeed, in order to overcome stomach complexation by phytates, the delay in stomach solubilization is defined as an efficiency factor within the scope of the invention. A zinc salt is considered more effective if it is solubilized more slowly. Results The results are presented in Table 1. Table 1: Percentage of dissolution of the premix of the invention and zinc oxide of the prior art Conclusion :

[0115] The ZnO-MgO premix of the invention makes it possible to significantly delay the solubilization of zinc, compared to conventional zinc oxides. The synergistic premix comprising a zinc oxide and a magnesium oxide improves the penetration of zinc through intestinal cells in vitro, and demonstrates better availability compared to a Zn sulfate, a Zn glycinate and a ZnO. The synergistic action between zinc and magnesium makes it possible to delay the solubilization kinetics of zinc and to limit its complexation by the organic matter of the ration at the stage of digestion in the stomach, in particular phytates. The premix of the invention therefore makes it possible to maximize the probability of absorption of zinc at the level of the duodenum by the synergy between zinc and magnesium, which acts as a support and a means of physical protection of zinc in the digestive tract.

[0116] Example 6: Absorption test on Caco2 cells of ore-melanae according to the invention ZnO-MaO, and comparison with the prior art The objective of this test is to determine the absorption of solubilized minerals on a differentiated cellular permeable intestinal membrane (Caco2). Samples were obtained following in-vitro digestion (IVD02) during which ileal juices were collected and used on cells. IVD allowed the evaluation of zinc solubilization for the control (ZnSO4), for a zinc glycinate, for a high specific surface area zinc oxide (ZnO HSS) and for the ZnO-MgO premix. Hizox® brand zinc sulfate, zinc glycinate, and high surface area zinc oxide were compared to the ZnO-MgO premix for this test to validate or invalidate our assumptions made when developing the specifications to achieve product performance. - Protocol Immortal tumor cells are cultured in an incubator. Multiplication takes place under controlled atmosphere, temperature, and light. Cells are placed on a membrane simulating the intestinal wall (0.4 μm). The test was carried out on Caco2 cultured on insert and differentiated into representative intestinal monolayers after 17 days. Ileal juices were deposited at the apical pole of the cells and after 60 minutes of incubation, the basal pole was removed entirely in order to measure the zinc concentration by ICP-MS. Results The results are presented in Table 2. Table 2: Zinc absorption on caco2 cells (mg / L) of the premix of the invention and zinc sources of the prior art The differentiated Caco2 cell test showed that zinc sulfate and high surface area zinc oxide are both absorbed at 0.5-1 mg / L while the use of zinc glycinate only allows zinc absorption limited to 0.275 mg / L. On the other hand, the inventive ZnO-MgO premix allows to reach 1.89 mg / L of total zinc absorbed on average. Three repetitions on this source were carried out.

[0117] Example 7: In vivo evaluation of the premix according to the invention ZnO-MqQ The effect of the premix of the invention on the performance and health of piglets in the Post-Weaning pre-starter stage (0-14 days post-weaning) was evaluated and compared to a standard oxide. The trial is conducted in accordance with appropriate quality standards. The experimental procedures used in this trial are approved by the RDN Animal Ethics Committee and are in accordance with Directive 2010 / 63 / EU of the European Parliament and Council and the Spanish recommendations for the care and use of animals for research (Boletin Oficial del Estado, 2013). Doses and products tested: This test was carried out with the premix according to the invention ZnO-MgO marketed under the brand CAPMAG®, at two levels of inclusion in the food and compared to a standard ZnO at a dose of 3261 ppm and a standard ZnO at a dose of 150 ppm. All rations are formulated in accordance with current regulations for piglets (FEDNA, 2013). The rations are distributed by RDN in the form of mash. The rations will be prepared by OCIPSA SIGLO XXI (Fuene de Cantos, Badajoz, Spain). All piglets receive a common commercial feed without innovative supplementation. The use of the product of the invention ZnO-MgO was compared with standard zinc oxide at nutritional dose as well as at pharmacological dose in the contents indicated in Table 3. Table 3: Concentrations used for each of the four modalities tested during the trial > Additive Zinc Content (ppm) Additive Content (ppm) Animals : A total of 288 piglets (Danbred x Duroc) weaned at 24 ± 5 ​​days of age were used for the trial. Each piglet was tagged, weighed, and allocated into groups of 8 piglets per pen. A total of 36 pens measuring 2.60 x 1.55 meters were considered for the trial. The pens were distributed within three identical rooms in a controlled environment. All pens were equipped with an individual feeder and a drinking nipple. The piglets were distributed per pen so as to have a similar average weight between the different pens, an equal distribution of males and females, and a personal space of 0.5 m 2 per piglet at 23 kg weight (in accordance with RD 53 / 2013). Any preventive treatment with antibiotics or antimicrobials is avoided before the start of the trial. The experimental conditions of the experimental building are automatically controlled according to the age of the piglet and adapted to commercial practices. Piglets are vaccinated against Mycoplasma and Circovirus. Measured parameters: Weight gain and feed consumption The weight of the piglets was measured from day 0 to day 42 post-weaning in order to record the daily weight gain and the total weight at the end of the test. The feed consumption of each animal was also recorded each day of the test and recorded as an average to assess the feed conversion ratio (FCR). The FCR corresponds to the feed conversion index (IC) in French. It is equal to average daily consumption relative to average daily weight gain. The results are presented in Table 4. The mean values ​​+ / - standard deviation are presented per treatment. Table 4: Effects of nutritional treatments on the growth performance of piglets from 0 to 42 days post-weaning. ZnO-MgO SEM P-value control Positive Negative Low High N=9 dose dose Live weight (kg) Day 0 6.74 6.75 6.73 6.77 0.076 0.997 Day 14 10.01 ab 9.61 b 10.31 a 10.33 a 0.169 0.022 Day 42 1 25.33 b 26.15 ab 27.01 ab 27.49 a 0.518 0.030 Pre-starter phase (Day 14 to Day 14 post-weaning) Average daily feed consumption 0.395 0.380 0.412 0.409 0.010 0.180 (kg / day) Average weight gain 0.233 ab 0.205 b 0.256 a 0.255 a 0.008 <.001 daily (kg / d) Feed conversion ratio l.705 b l,863 a l,617 b l,613 b 0.034 <.001 (kg / kg) Starter Phase (D15 to D42 post-weaning) 1 Average weight gain 0.571 b 0.611 ab 0.621 a 0.618 a 0.011 0.013 daily (kg / day) Overall period (Day 42 to Day 42 post-weaning) 1 Daily weight gain 0.444 b 0.463 ab 0.486 a 0.482 a 0.009 0.011 (kg / day) _ 1 The live weights of piglets euthanized on D14 of the trial for ileal tissue analyses were removed from the data set used for growth performance results analyzed from D15 to D42 post-weaning. Analysis of results: Piglets receiving the ZnO-MgO product have higher live weights than piglets receiving standard ZnO at nutritional dose, but also than those receiving standard ZnO at pharmacological dose. The product of the invention ZnO-MgO significantly improved the average daily weight gain. The addition of ZnO-MgO showed no impact on the piglets' feed consumption. The use of ZnO-MgO premix as a source of zinc in the premix significantly improved the feed conversion ratio compared to the negative control. Piglets fed ZnO-MgO continue to gain more weight daily in the starter phase following the pre-starter supplementation phase. Thus, the use of ZnO-MgO as a supplement in the pre-starter phase has a prolonged impact on the animal. Fecal analysis: Analyses of feces after 14 days of use of the different treatments made it possible to assess the quantity of zinc not used by the animal and thus released into the soil, contributing to pollution. The results are presented in Figure 1. The use of the ZnO-MgO mixture in post-weaning piglets during this in vivo trial resulted in a reduction in the release of zinc into the soil. The content measured in the feces was 450 ppm and 697 ppm for the low dose (L ZnO-MgO) and high dose (H ZnO-MgO) of the premix, respectively. These amounts of zinc are lower than the 925 ppm released by piglets supplemented with standard ZnO. Example 8: Dissolution kinetics of the product of the invention and of a comparative product, in an acid medium The kinetics of pH evolution over time of the product according to Example 1 was compared with that of a comparative product. Products reviewed: The product of Example 1 was obtained by heating to a temperature of 1000°C a powdery mixture of a magnesium oxide raw material and a trace element oxide raw material. The comparative product was obtained by mixing at room temperature a powdered raw material of magnesium oxide and a powdered raw material of a trace element oxide. The comparative product was identical to the raw material mixture that was used to prepare the product of Example 1. The comparative product therefore did not undergo any heat treatment at a temperature above 700°C. Dissolution protocol: The dissolution protocol is identical to that described above. Results : The results are shown in Figure 2, the dotted curve corresponding to a mixture not in accordance with the invention. The evolution of pH is directly correlated to the solubilization of the crystalline phases present in the hydrochloric medium. Thus, the kinetics of pH evolution makes it possible to follow the kinetics of Zn release 2+ (and therefore Mg 2+) in the reaction medium. The non-solubilization of the premix of the invention (solid curve) between 0 and 60 seconds is followed by a delay extending up to 200 seconds of reaction, which makes it possible to envisage a bypass with respect to the antagonists in the digestive tract. On the other hand, we observe that a comparative product, which is not in the form of a ternary solid - comprising a zinc oxide and a magnesium oxide and presenting two different crystalline forms (dotted curve) - does not cause a delay in dissolution and undergoes very rapid, almost instantaneous solubilization in an acid medium.

Claims

Claims

1. A synergistic premix for animal nutrition, said premix comprising a ternary solid of magnesium, a trace element and oxygen, said trace element being selected from iron, copper, zinc and manganese.

2. Synergistic premix according to claim 1, characterized in that the ternary solid is a solid solution of substitution of the trace element in a magnesium oxide.

3. Synergistic premix according to claim 1, characterized in that the trace element represents from 10% to 45% by mole of the ternary solid.

4. A method of manufacturing a synergistic premix for animal nutrition, said method comprising a step of heating, at a temperature ranging from 700°C to 1500°C, a mixture comprising at least one powdery raw material of a magnesium oxide, and at least one powdery raw material of a trace element.

5. A manufacturing method according to claim 4, characterized in that the value of the particle size of the raw material of a magnesium oxide and the value of the particle size of the raw material of a trace element are less than 200 microns.

6. A manufacturing method according to claim 4 or 5, characterized in that the purity of the raw material of a magnesium oxide and the purity of the raw material of a trace element are greater than 95% by mass.

7. Manufacturing method according to one of claims 4 to 6, characterized in that the powdery raw material of a magnesium oxide is chosen from a magnesia MgO, a magnesium carbonate, a magnesium hydroxycarbonate, a magnesium sulfate, a magnesium phosphate, a magnesium chloride, a magnesium hydroxide or one of their hydrates.

8. Manufacturing method according to one of claims 4 to 7, characterized in that the powdery trace element raw material is a raw material of a trace element oxide comprising a compound chosen from ZnO, ZnCO3,

9. Manufacturing method according to one of claims 4 to 8, characterized in that the powdery raw material of a magnesium oxide is a magnesia whose particle size value is characterized by a D50 of less than 100 microns.

10. Synergistic premix for animal nutrition obtainable by the process according to one of claims 4 to 9.

11. Use of the synergistic premix according to one of claims 1, 2, 3 or 10 for producing at least one biological effect in a non-human animal, said biological effect being chosen from increasing the weight gain of the animal, supporting animal growth, improved feed efficiency, improved feed conversion ratio and support for nutrient assimilation.

12. Use according to the preceding claim, characterized in that the non-human animal is chosen from livestock, racing animals, and domestic animals, such as for example poultry, crustaceans, fish, dogs, cats, horses, rabbits, sheep, goats, ruminants and pigs.

13. A nutritional supplement for a non-human animal comprising the premix according to one of claims 1, 2, 3 or 10, and a compound chosen from vitamins, probiotics, macroelement salts, trace element salts, enzymes and amino acids.

14. A method of preparing a feed ration for a non-human animal, comprising a step of dry incorporation of the premix according to claim 1, 2, 3 or 10 with fodder and / or cereals.

Images